Giving dental restorative materials antimicrobial properties has long been known and is usually carried out by the purely physical mixing of an antimicrobial active ingredient into a corresponding material matrix. Thus for example in WO 98/48766 and correspondding US published application US2002012634, which is hereby incorporated by reference, tooth-coating material for the prevention of caries is described which contains triclosan (2,4,4′-trichloro-2′-hydroxydiphenylether) as antimicrobial active ingredient. Materials for dental use such as prosthetic plastics and fixing cements which contain antimicrobial phenolic substances such as triclosan are also described in US 2003/0220416, which is hereby incorporated by reference.
DE 19813686 and corresponding U.S. Pat. No. 6,162,056, which is hereby incorporated by reference, disclose a gutta-percha-based root-canal filling material which releases chlorhexidine as antimicrobial active ingredient.
Several problems are associated with the purely physical mixing of antimicrobial active ingredients into a material. In order to achieve its antimicrobial effect, the active ingredient must be released over the period of action of the material. As a rule, the release rates are such that the active ingredient is initially released in a very high concentration and thereafter the antimicrobial effect is largely lost. Another disadvantage is that toxic side-effects can occur at high active ingredient concentrations, which is undesirable in particular in medical applications. For this reason, there has been a switch, for such applications in particular, to making the active ingredient polymerizable in order to immobilize it during the curing of the material by homopolymerization or copolymerization with another polymerizable monomer in the forming polymer.
U.S. Pat. No. 5,536,861 and U.S. Pat. No. 5,358,688, which are hereby incorporated by reference, disclose organosilicone monomers which contain a quaternary ammonium group as antimicrobial group for use in contact lenses.
EP 0663409 and corresponding U.S. Pat. No. 5,520,910, which is hereby incorporated by reference, discloses monomers which contain quaternary phosphonium groups as active group for use in contact lenses.
In EP 0537774, and corresponding U.S. Pat. No. 5,408,022 and U.S. Pat. No. 5,494,987, which are hereby incorporated by reference, polymerizable active-ingredient monomers which contain a quaternary ammonium group are described. (Meth)acryl functionalities are used as polymerizable group, an alkylene spacer with 2 to 18 C atoms being located between the polymerizable group and the active group.
In EP 0705590 and corresponding U.S. Pat. No. 5,733,949, which is hereby incorporated by reference, and WO 01/90251, special compositions for dental use which contain an antimicrobial, polymerizable monomer according to EP0537774 and corresponding U.S. Pat. No. 5,408,022 and U.S. Pat. No. 5,494,987, are described.
A disadvantage when using polymerizable active ingredient monomers is that in most cases only the monomer has an antimicrobial effect, which is lost after the polymerization. Often, only residual monomer present is responsible for the antimicrobial effect of the polymers, with the result that after the elution of the non-polymerized antimicrobial monomers the antimicrobial effect of the materials diminishes. The antimicrobial long-term effect is thus significantly reduced, as a result of which e.g. drugs or medicinal products lose at least some of their clinical capability.
EP 1849450 and corresponding US Published Application 2007254979, which is hereby incorporated by reference, discloses dental materials equipped with an antimicrobially active macromer wherein an antimicrobially active group is bonded to a radically polymerizable group via a polymeric spacer and which displays a high anti-microbial efficacy also after polymerization.
U.S. Pat. No. 6,316,015, which is hereby incorporated by reference, describes substrates to the surfaces of which molecules with antibiotic, bactericidal, virucidal or fungicidal properties are covalently bonded, such as e.g. catheters, syringes, needles and tubes for medical applications.
EP 1707601 and corresponding US Published Application 2008226585, which is hereby incorporated by reference, describes a method of treating surfaces, wherein a statistical copolymer is bonded to the surface in order to give the latter cytotoxic or cell-adhesion properties. The statistical copolymer has at least one monomer unit A, the reactive site of which can form covalent bonds with the substrate, and a monomer unit B, which comprises at least one antimicrobial, antiviral or fungicidal molecule. The method is said to be useful for the antiseptic treatment of various substrates, such as for example plastics, wood, paper or textiles and in particular in the field of personal hygiene, in the clinical field as well as for domestic use and in the food industry.